The proposed research will combine virologic, light and electron microscopic, immunofluorescent and immunologic methods to study in vivo and in vitro demyelination caused by viruses. (1) Studies of JHM virus - induced demyelination will continue particularly the chronic demyelination. Further attempts to clarify the mechanisms of disease will be studied in vitro. (2) Work will continue on human papovaviruses particularly isolates from progressive multifocal leukoencephalopathy (PML). Primate work in attempting to establish an animal model will progress and studies of cells derived from the brains of PML patients will be continued. (3) Attempts will be made to identify and isolate viruses from selected human biopsies and autopsy tissue utilizing in vitro methods.